Adrenal regeneration hypertension (ARH) is a form of experimental hypertension produced by injuring the adrenal gland of the rat and is believed to be produced by increased secretion of mineralocorticoids. Deoxycorticosterone has been shown to play an important role but cannot fully explain the syndrome. We have isolated a new powerful mineralocorticoid, 19-nor-deoxycorticosterone, and three precursors (19-hydroxy-deoxycorticosterone, 19-oxo-deoxycorticosterone, and 19-oic-deoxycorticosterone). In this proposal we plan to elucidate the role of these four steroids by completing the development of radioimmunoassays and using them to measure the steroids during the development of ARH. The steroids will be injected chronically into rats to study whether they induce hypertension. The biosynthesis of 19-OH-DOC, 19-oxo-DOC and 19-oio-DOC in the adrenal will be investigated and the site of synthesis 19-nor-DOC localized. We will study the ability of these compounds to bind Type I, II, and III renal corticoid receptors and investigate the possibility of additional types of receptors using the tritiated steroids we have synthesized. We will measure the ability of plasmas to displace(3H)-aldosterone from its renal receptor to provide evidence of increased total mineralocorticoid activity and/or unexplained activity in plasmas during development of ARH in comparison to controls. In this way we will determine the relative importance of each steroid at the various stages of ARH.